Developing a highly sensitive, reproducible and robust molecular assay has always been a challenge in the molecular diagnostics world, from balancing the sensitivity and specificity of a test to maximizing the concentration of analytes in low-volume samples. Much effort has been made to develop and validate different technologies to meet this end. However, with a vast number of diagnostics tests available on the market comes the need of standardization among these tests and the knowledge of how different technology or approach might affect the results. Cambridge Healthtech Institute’s 6th Annual Sample Prep, Assay Development, and Validation program is designed to bring together experts in the field to share their latest advances and consensus for best practices in sample preparation and assay development for advanced molecular diagnostics technologies.

Final Agenda

Arrive Early for:


SC3: NGS Assay Selection, Validation and Compliance - Detailed Agenda


SC14: Liquid Biopsy Technologies and Applications - Detailed Agenda


SC17: Next-Generation Sequencing as a Diagnostics Platform - Detailed Agenda

Monday, March 11

10:30 am Conference Program Registration Open (South Lobby)


11:50 Chairperson’s Opening Remarks

L. James Lee, PhD, Helen C. Kurtz Professor, Department of Chemical and Biomolecular Engineering, the Ohio State University

12:00 pm KEYNOTE PRESENTATION: A PDX/Organoid Biobank of Advanced Prostate Cancer for Disease Modeling and Therapeutic Screening

Kathleen KellyKathleen Kelly, PhD, Lab Chief, Laboratory of Genitourinary Cancer Pathogenesis, Center for Cancer Research, National Cancer Institute

Organoid cultures provide a technology to culture epithelial cancers that otherwise do not propagate in vitro. We have established a preclinical platform of PDX- and patient biopsy-derived metastatic castrate resistant prostate cancer (mCRPC) organoids that is experimentally facile for high throughput and mechanistic analysis. The genetic and phenotypic variability and stability of models, genetic manipulations, and the utility of such a platform for drug sensitivity determination will be discussed.

12:30 Extracellular Vesicular RNAs for Cancer Diagnosis and Therapy

Lee_JamesL. James Lee, PhD, Helen C. Kurtz Professor, Department of Chemical and Biomolecular Engineering, the Ohio State University

We have developed facile biochip technologies to detect target microRNAs and mRNAs in individual extracellular vesicles (EVs) using advanced molecular beacons designs and nanoparticles. These biochip technologies have been successfully applied to detect and manipulate EV RNAs for cancer diagnosis in liquid biopsy and potentially for cancer therapy.


1:00 Enjoy Lunch on Your Own


2:30 Chairperson’s Remarks

L. James Lee, PhD, Helen C. Kurtz Professor, Department of Chemical and Biomolecular Engineering, the Ohio State University

2:40 High-Yield Isolation and Quantification of Exosomes and Exosomal miRNA

Hsueh-Chia_ChangHsueh-Chia Chang, PhD, Bayer Corporation Professor of Chemical Engineering, Chemical and Biomolecular Engineering, University of Notre Dame

False positives are major hurdles for blood screening tests and companion diagnostics based on miRNA over-expression. Our bench-marking studies confirm that they are caused by intrinsic heterogeneities of their exosomal vehicles and low yields during two sample pretreatment steps: exosome/miRNA extraction and ligation-based reverse-transcription for PCR quantification. We present validated isolation, lysing and PCR-free quantification technologies and propose a new single-exosome assay to resolve these issues.

3:10 Microfluidic Engineering of Exosomes: Editing Cellular Messages for Precision Therapeutics

Mei_HeMei He, PhD, Assistant Professor, Chemical & Petroleum Engineering, Chemistry, University of Kansas

Study of extracellular vesicles (EVs), particularly exosomes, holds significant promise; however, it is technically challenging to define these small and molecularly diverse nanovesicles. With intrinsic molecular payload and biodegradability, molecular engineering of exosomes opens new avenues for mediating cellular responses and developing novel nano-delivery systems in precision therapeutics. Microfluidic lab-on-chip technology is playing pivotal roles in this emerging field. Advancements of microfluidic technology for engineering exosomes and assessed future applications and perspectives in developing precision therapeutics will be discussed.

3:40 Microfluidic technologies are taking point-of-care testing to the next level

Clerc_SébastienSébastien Clerc, Technology & Market Analyst |Microfluidics & Medical Technologies | Life Sciences & Healthcare Division, Yole Développement

The field of microfluidic-based point-of-care testing devices is enjoying nice dynamics and the pace at which new products are being commercialized is accelerating. Numerous fundraising operations, collaborations and mergers and acquisitions occur: the supply chain is structuring at a rapid pace as the market is booming ($3.5B in 2017, expected to reach $13.2B by 2023). Historically, assays with more complex procedural steps were reserved for central labs to carry out, but over the last decade companies have leveraged microfluidic technologies to integrate all the required steps into single cartridges that can perform multiple tests in parallel. In this talk, Yole’s analyst will share his view of the microfluidic market and technology, highlighting how such micro-structured devices enable new possibilities within the diagnostics industry in terms of automation, miniaturization, and integration of complex steps. Moreover, he will explain the remaining challenges that the players will face in the coming years along with the main market trends.

4:10 Networking and Q & A with Speakers in the Session

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session  (Room Location: 3 & 7)

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, March 12

7:30 am Registration Open and Morning Coffee (South Lobby)

8:00 Plenary Keynote Session   (Room Location: 3 & 7)

9:15 Refreshment Break in the Exhibit Hall with Poster Viewing


10:15 Chairperson’s Remarks

Karl V. Voelkerding, MD, Professor, Pathology, University of Utah; Medical Director for Genomics and Bioinformatics, ARUP Laboratories

10:25 Best Practices for Clinical Validation of NGS Bioinformatics Pipeline

Somak_RoySomak Roy, MD, Director, Molecular Informatics, Genetics Services, & MGP fellowship, Molecular and Genomic Pathology, University of Pittsburgh Medical Center

A joint consensus guideline was developed by the Association of Molecular Pathology (AMP), in conjunction with the College of American Pathologists (CAP), and the American Medical Informatics Association (AMIA) for validation of clinical NGS bioinformatics pipelines. This talk will discuss these best practice consensus recommendations with emphasis on distributive NGS testing model, role of in silico datasets, and laboratory accreditation checklist (CAP).

10:55 Improving Clinical Quality with Bioinformatics Automation

Gee_Elaine_SMPElaine P.S. Gee, PhD, Founder & President, BigHead Analytics Group; Principal Algorithm Development Engineer, Sensor R&D, Diabetes R&D, Medtronic

Clinical genomic testing relies on complex bioinformatics pipelines to perform a range of genomic profiling functions, from identification of germline and somatic genomic alterations to pathogen detection and identification. Each pipeline is comprised of complex algorithms carefully parameterized to meet the intended clinical needs. This talk highlights how to improve quality at scale by leveraging automation throughout the bioinformatic product life cycle for actionable feedback on pipeline performance.

11:25 Current and Future Approaches to Sequence Variant Interpretation

Eggington_Julie_SMPJulie M. Eggington, MS, PhD, Co-Founder and CEO, Center for Genomic Interpretation (CGI)

The clinical science speciality of genetic variant classification and reclassification has evolved rapidly in recent years. With a focus on germ line (aka hereditary) disease variant classification, this presentation will review the current state of the speciality, including what is working well, and what can and will be improved to ensure better patient care.

Sanguine_Biosciences11:55 Longitudinal Sampling & Data Collection using Home Visits & Mobile Technology 

Brian Neman, MS, CEO, Sanguine Biosciences, Inc.

12:25 pm Enjoy Lunch on Your Own

1:35 Refreshment Break in the Exhibit Hall with Poster Viewing


2:05 Chairperson’s Remarks

Jennifer J.D. Morrissette, PhD, FACMG, Scientific Director, Clinical Cancer Cytogenetics; Clinical Director, Center for Personalized Diagnostics, Department of Pathology, University of Pennsylvania

2:10 NCI Resources to Support Biospecimen-Based Research

Moore_HelenHelen M. Moore, PhD, Branch Chief, Biorepositories and Biospecimen Research Branch, NCI

The U.S. National Cancer Institute offers evidence-based best practice documents, an online literature and SOPs database, and research programs to support the collection of high quality research biospecimens. These resources will be discussed as well as new biobanking programs being developed under the Cancer Moonshot initiative.

2:40 A Moving Target: Optimization and Evolution of NGS Testing in Myeloid Malignancies

Morrissette_JenniferJennifer J.D. Morrissette, PhD, FACMG, Scientific Director, Clinical Cancer Cytogenetics; Clinical Director, Center for Personalized Diagnostics, Department of Pathology, University of Pennsylvania

This talk will discuss how our laboratory incorporated longitudinal testing for our hematological malignancy patients, based on data demonstrating the shift of clones containing variants that respond to targeted therapies, including FLT3, IDH1 and IDH2. The extremely poor outcome for patients harboring a TP53 mutation and the gene variants known to respond to targeted therapies has highlighted the need to rapidly identify variants. The final section will discuss the validation of a rapid NGS test in the laboratory.

3:10 A Multi-Institutional Collaborative Approach to Reducing Costs and Driving Standardization of Oncology NGS

Segal_JeremyJeremy Segal, MD, PhD, Assistant Professor; Director, Genomic and Molecular Pathology, University of Chicago

Next-generation sequencing (NGS) oncology diagnostics are continuing to grow in complexity and represent a substantial developmental and validation challenge for clinical laboratories. Academic laboratories are mainly working independently, creating a variety of different assays on various chemistry platforms with variable gene lists, bioinformatics algorithms and reported features. This assay variability raises questions of cross-site concordance and puts academic labs at a regulatory disadvantage. To lower NGS-associated laboratory costs and begin to work towards cross-site assay standardization, we assembled a collection of 17 academic laboratories to pursue a novel type of large-scale hybrid capture reagent purchase capable of supporting standardization efforts while permitting flexible design for site-specific gene content. This talk will address the formation of the Genomic Oncology Academic Laboratory (GOAL) consortium, the details of the group purchase including design specifications and performance, and future directions related to assay and bioinformatics standardization.

3:40 Tissue Print Technologies for Biopsy-Based  Molecular Biomarker Studies

Sandra M. Gaston PhD, Director, Molecular Biomarkers Analytic Laboratory, Radiation Oncology, University of Miami Miller School of Medicine

Many tissue biomarker tests are designed to use FFPE specimens as a source of RNA and/or DNA, but the allocation of FFPE tissue for pathology and research is becoming increasingly challenging, particularly for biopsy specimens. Tissue prints provide a practical alternative for obtaining RNA, DNA and protein biomarkers for molecular analyses without compromising the specimen for diagnostic H&E and immunohistochemistry.  With biopsies, tissue prints support molecular biomarker studies of valuable specimens that may otherwise be significantly limited or entirely unavailable for research. Because tissue prints are snap frozen rather than fixed in formalin, the purified tissue print RNA and DNA is of  high quality and suitable for advanced biomarker analysis. We will review applications of tissue print techniques to biopsy-based studies of RNA, DNA and protein biomarkers, to molecular biomarker mapping and to biorepository specimen annotation.

4:10 St. Patrick’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

6:00 Close of Day

Wednesday, March 13

7:30 am Registration Open and Morning Coffee (South Lobby)

8:00 Plenary Keynote Session   (Room Location: 3 & 7)

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

1 & 2

10:50 Chairperson’s Remarks

David B. Roth, MD, PhD, Director, Penn Center for Precision Medicine; Chair, Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania

11:00 Precision Oncology in AML: Choosing the Right Drugs to Treat

Cherry_SaraSara Cherry, PhD, Professor of Microbiology, Scientific Director, High-throughput Screening Core; Director, Program for Chemogenomic Discovery, University of Pennsylvania

Acute myeloid leukemia (AML) is the most common form of adult acute leukemia, with ~16,000 new cases per year in the US and 10,000 deaths. Despite intensive treatment regimens, the 5-year survival is ~35%. New targeted therapies have shown promise, but are not curative, and only available to subsets of patients. We developed a new pipeline to directly screen patient tumor cells for sensitivity to 3000 clinically actionable drugs and are currently developing this into a diagnostic for personalized therapies in AML.

11:30 Personalized Cancer Models for Target Development and Precision Oncology

Kemp_Chris_PRXChristopher Kemp, PhD, Full Member, Human Biology, Fred Hutchinson Cancer Research Center

A major goal of precision oncology is to utilize genomic information to inform patient care. While there are spectacular examples of success, for the great majority of cancer patients, genomic information is insufficient to guide patient care or select effective therapeutic options. We have developed an approach that employs high-throughput functional testing with both siRNA and drugs using patient tumor cell cultures. This functional data combined with genomic analysis is used to distinguish driver from passenger mutations and identify novel drug targets and potentially effective drugs specific to a given patient.

12:00 pm Functional Approaches to Define Tumor Intrinsic and Extrinsic Targets for Personalized Therapeutic Regimens

Tyner_JeffJeffrey Wallace Tyner, PhD, Associate Professor, Developmental & Cancer Biology, Oregon Health & Science University (OHSU) Knight Cancer Institute

To overcome these obstacles in delivery of precision medicine based on genomic-only approaches, my research program has developed a pipeline of functional tools for analysis of primary cells from patients with hematologic malignancies. This pipeline is comprised of siRNA, CRISPR/Cas, and small-molecule libraries to interrogate the genes and signaling pathways required for cancer cell growth. Simultaneous application of these functional approaches with genomic data has accelerated our understanding of pathways that contribute to neoplasia. In addition, these assays are completed in a clinically relevant time frame of three days, such that the data from these assays can be used to directly inform therapeutic strategies, even in the absence of genomic information.

12:30 Enjoy Lunch on Your Own

1:10 Refreshment Break in the Exhibit Hall and Last Chance for Poster Viewing


1:50 Chairperson’s Remarks

Muhammed Murtaza, MD, PhD, Assistant Professor, Co-Director, TGen Translational Genomics Research Institute

2:00 Evaluation of Reference Samples for Validation of Circulating Tumor DNA Assays

Murtaza_MuhammedMuhammed Murtaza, MD, PhD, Assistant Professor, Co-Director, TGen Translational Genomics Research Institute

Several new technologies are being developed for accurate detection and quantification of circulating tumor DNA in plasma. To aid assay development, analytical validation and comparison with existing methods, reference samples with known mutations that mimic cell-free circulating DNA are critical. I will present our experience with assay development and the utilization of reference samples in this process.

2:30 Validation of MSK-ACCESS for Liquid Biopsies

BRANNON_A_ROSEA. Rose Brannon, PhD, Senior Computational Biologist, Pathology, Memorial Sloan Kettering Cancer Center

MSK-ACCESS is a clinical error-corrected next-generation sequencing assay for genomic profiling of cell-free DNA for cancer patients at Memorial Sloan Kettering Cancer Center. For validation, more than 60 patient samples were analyzed with this assay, confirmed mutations were detected down to 0.1% allele frequency, and assay reproducibility samples demonstrated reliability. MSK-ACCESS identifies clinically actionable mutations using less invasive techniques, reducing the need for biopsies.

3:00 Development, Validation, and Clinical Implementation of cfDNA Assays in Oncology

Minetta_LiuMinetta C. Liu, MD, Research Chair, Oncology, Mayo Clinic

Tumor-specific molecular alterations increasingly play a part in drug selection and prognosis. Technologies that allow for the detection of specific mutations in cell-free DNA (cfDNA) isolated from the peripheral blood have led to the concept of “liquid biopsies”. This has immediate applications with potential utility in multiple solid tumor malignancies. This session will discuss efforts to validate these molecular biomarkers and develop solutions to promote rapid translation into clinical practice.

3:30 Session Break


3:40 Chairperson’s Remarks

Kurt A. Schalper, MD, PhD, Assistant Professor, Pathology and Medicine (Medical Oncology); Director, Translational Immuno-Oncology Laboratory, Yale Cancer Center

3:45 Deconvoluting Cellular Determinants of Anti-Tumor Immune Recognition

Ash AlizadehAsh Alizadeh, PhD, Associate Professor of Medicine, Divisions of Oncology & Hematology, Stanford University School of Medicine

I will discuss our work on developing techniques to characterize the cellular organization of tumor microenvironments, with a focus on compositional diversity and clinical significance of hematopoietic cell subsets. I will describe the genesis and application of deconvolution algorithms to resolve tumor subpopulations and cell type-specific expression programs from genomic profiles of diverse human tumors. I will discuss the clinical translational potential in the context of individualized approaches to immuno-oncology.

4:15 Development and Validation Considerations for Clinical Laboratory Methods for Mutational Burden Determination

eric-konnickEric Konnick, MD, MS, Assistant Professor; Associate Director, Genetics and Solid

Tumors Laboratory, University of Washington

Recent studies have indicated that increased mutational burden and microsatellite instability may predict response to anti-cancer therapies targeting the immune system. Many pre-analytical, analytical, and design factors may contribute to the ability of a clinical diagnostic test to appropriately measure the biomarker of interest. A thorough understanding of the relevant factors that can impact patient results will allow an appropriate comparison of existing methods and implementation of new assays.

4:45 Development and Validation of a Deep Learning Algorithm for PD-L1 Scoring in Tumour Cells and Immune Cells

Vandenberghe_MichelMichel Vandenberghe, PharmD, PhD, Senior Scientist, Precision Medicine Labs, Precision Medicine and Genomics, IMED Biotech Unit, AstraZeneca

Treatment decisions in oncology are commonly informed by the visual assessment of immunohistochemistry (IHC) biomarkers (such as PD-L1 expression) by pathologists. However, pathology services face mounting pressure as diagnostic demand increases and workforce decreases. Digital pathology and artificial intelligence have the potential to streamline the diagnostic workflow thereby improving pathologists' workload, accelerating turn-around-times and facilitating access to testing. Here, we report the in-house development and analytical validation of a deep learning algorithm for automated scoring of PD-L1 expression in samples processed with the VENTANA PD-L1 (SP263) Assay. The algorithm was trained to score PD-L1 expression in tumour cells and in immune cells using 29318 manually annotated cells across a set of 150 PD-L1 IHC images from 30 urothelial carcinoma (UC) samples. The algorithm was then validated in an independent cohort of UC samples. In the validation cohort, the algorithm demonstrated high inter-scan reproducibility (99% overall percent agreement, N=197), high inter-scanner reproducibility (100% overall percent agreement, N=33) and substantial agreement with pathologist-based scoring of PD-L1 expression (84% overall percent agreement, N=195). In conclusion, this study shows that our deep learning algorithm has favourable analytical characteristics to assist pathologists in scoring PD-L1 in both tumour cells and immune cells.

4:55 Multiparametric Flow Cytometry Analysis of Checkpoint Inhibitors (PD-1 and PD-L1) in Dissociated Tumor and Normal Tissues

Fahl_ShawnShawn Fahl, PhD, Senior Research Scientist, Research & Development, Discovery Life Sciences

Immune checkpoint inhibitors, such as anti-PD-1 and anti-PD-L1, have been approved as first or second-line therapies in melanoma, lung cancer, renal cancer, and urothelial cancer. More recently, these therapies have been approved in MSI-high colorectal cancer. In the Discovery Life Sciences clinical network, we observe high percentages of patients on PD-1 and PD-L1 immunotherapies across the relevant indications. However, despite these successes, there are still some patients that have no or partial remission in response to these therapies. Understanding the expression of checkpoint inhibitors within the complex cellular components of the tumor microenvironment provides not only crucial information on the potential functionality of these therapies, but also allows for the identification of potential companion diagnostic markers to stratify patients prior to treatment. We present below our initial exploration of these markers in our dissociated tumor and normal tissues via multiparametric flow cytometry to evaluate their expression on cellular subsets in both cancerous and non-cancerous tissues.

5:05 Tumor Mutational Burden (TMB) Analysis Using an Ultra-High Multiplexed 20,000-Amplicon NGS Panel in a Rapid 4-Hour Workflow

Pendleton_KathrynKathryn Pendleton, PhD, Scientist, Paragon Genomics, Inc.

Tumor mutational burden (TMB) is currently gaining significant importance in the field of immuno-oncology due to its correlation with patient response to checkpoint inhibitor chemotherapy. Traditionally, TMB is calculated using whole exome sequencing via laborious hybrid-capture based methods. However, targeted sequencing approaches provide better coverage of the genetic regions of interest at lower costs. Here we present an ultrafast, 4-hour method for preparing target enriched NGS libraries for assessing TMB - the CleanPlex® technology. This method would streamline and lower the cost of immuno-oncology studies. This is a multiplex-PCR-based technology, that provides a highly efficient, accurate and robust method for unbiased enrichment of tens of thousands of target regions while minimizing non-specific primer-primer interactions and GC bias and maximizing coverage uniformity.

5:15 Close of Conference Program

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MARCH 14-15

TS4: Introduction to Liquid Biopsy for Cancer - Detailed Agenda

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March 26-27, 2024

AI in Precision Medicine

Implementing Precision Medicine

At-Home & Point-of-Care Diagnostics

Liquid Biopsy

Spatial Biology

March 27-28, 2024

AI in Diagnostics

Diagnostics Market Access

Infectious Disease Diagnostics

Multi-Cancer Early Detection

Single-Cell Multiomics